A leading cause of mortality within the developed world is cardiovascular disease. Coronary disease is of significant concern. Patients having such disease have narrowing in one or more coronary arteries. Generally, however, patients have narrowing in multiple coronary arteries. One treatment for the narrowing is stenting the blood vessel. Stenting involves the placement of a stent at the site of acute artery closure. This type of surgery has proved effective in restoring vessel patency and decreasing myocardial ischemia. However the exposure of currently used metallic stents to flowing blood can result in thrombus formation, smooth muscle cell proliferation and acute thrombotic occlusion of the stent.
Drug eluting stents (“DES”) generally result in lower restenosis and revascularization rates as compared to bare metal stents in vessels having a diameter greater than approximately 3.0 mm (“large vessels”). However, vessels having a diameter of less than or less than 3.0 mm (“small vessels”) continue to be clinically and angiographically at a disadvantage to larger vessels due to the inability of the small diameter to accommodate neointimal hyperplasia. These small-vessel DES have not led to significantly reduced late loss diameter or percent diameter stenosis like their large-vessel DES counterparts.
A safety concern associated with drug-eluting stents is the occurrence of stent thrombosis. For example, the polymer coatings and other aspects of DES may result in increased thrombogenicity. Dual antiplatelet therapy (DAPT), the administration of two anti-platelet medications, e.g., aspirin plus a P2Y12 receptor inhibitor such a thienopyridine (clopidogrel or prasugrel) or a non-thienopyridine (ticagrelor), is one accepted strategy for minimizing the risk of stent thrombosis. To mitigate such risk, the American College of Cardiology Foundation (ACC)/American Heart Association (AHA) Task Force/Society for Cardiovascular Angiography and Interventions (SCAI) guideline recommends patients having percutaneous coronary intervention receive DAPT therapy prior to stent implantation, followed by twelve months of DAPT after the procedure. (See, e.g., Jneid H, Anderson J L, Wright R S, Adams C D, Bridges C R, Casey D E Jr, Ettinger S M, Fesmire F M, Ganiats T G, Lincoff A M, Peterson E D, Philippides G J, Theroux P, Wenger N K, Zidar J P. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/non-ST-elevation myocardial infarction (UA/NSTEMI) (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol 2012; 60:645-81.) (the “Guidelines”) The Guidelines recommend a loading dose of P2Y12 receptor inhibitor therapy for UA/NSTEMI patients for whom percutaneous coronary intervention (“PCI”) is planned. The Guideline further recommend that one of the following regimens should be used: Clopidogrel 600 mg should be given as early as possible before or at the time of PCI; or prasugrel 60 mg should be given promptly and no later than 1 hour after PCI once coronary anatomy is defined and a decision is made to proceed with PCI; or ticagrelor 180 mg should be given as early as possible before or at the time of PCI.
The literature also suggested that the premature discontinuation of DAPT is also associated with stent thrombosis. Therefore, to mitigate the risk of stent thrombosis, the Guidelines further recommend patients who receive a DES be given aspirin indefinitely and a P2Y12 receptor inhibitor for at least 12 months in the absence of increased risk of bleeding. The following duration and maintenance dose of P2Y12 receptor inhibitor therapy is recommended: In UA/NSTEMI patients undergoing PCI, either clopidogrel 75 mg daily, prasugrel 10 mg daily, or ticagrelor 90 mg twice daily should be given for at least 12 months.
In real-world practice, however, many patients do not receive antiplatelet therapy at the time of stent implantation. In addition, non-compliance with the continuation of DAPT therapy after the procedure occurs, e.g., due to adverse events, invasive surgery, patient non-compliance with the prescribed therapy, etc. Most significantly, patients do not receive antiplatelet therapy at the site of the stent implantation. Rather, patients orally ingest a quantity of medication that is not targeted to the location of the potential thrombosis. Thus, there remains a need in the art for devices and methods for the addressing this concern, e.g., devices and system capable of delivering loading dose of DAPT at the site of stent deployment and providing a maintenance dose of DAPT at the site of stent deployment for a certain time following the procedure.